J.Matthews_paper_for discussion1 - A NTIMICROBIAL AGENTS...

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Unformatted text preview: A NTIMICROBIAL AGENTS AND CHEMOTHERAPY, Dec. 2009, p. 50465054 Vol. 53, No. 12 0066-4804/09/$12.00 doi:10.1128/AAC.00774-09 Copyright 2009, American Society for Microbiology. All Rights Reserved. Characterization of a New Metallo- -Lactamase Gene, bla NDM-1 , and a Novel Erythromycin Esterase Gene Carried on a Unique Genetic Structure in Klebsiella pneumoniae Sequence Type 14 from India Dongeun Yong, 1,2 Mark A. Toleman, 2 Christian G. Giske, 3 Hyun S. Cho, 4 Kristina Sundman, 5 Kyungwon Lee, 1 and Timothy R. Walsh 2 * Yonsei University College of Medicine, Research Institute of Antimicrobial Resistance, Seoul, Republic of Korea 1 ; Department of Medical Microbiology, Cardiff University, Cardiff, United Kingdom 2 ; Clinical Microbiology, MTCKarolinska Institutet, Karolinska University Hospital, Stockholm, Sweden 3 ; Yonsei University College of Life Science and Biotechnology, Seoul, Republic of Korea 4 ; and Department of Clinical Microbiology, O rebro University Hospital, O rebro, Sweden 5 Received 10 June 2009/Returned for modification 7 August 2009/Accepted 10 September 2009 A Swedish patient of Indian origin traveled to New Delhi, India, and acquired a urinary tract infection caused by a carbapenem-resistant Klebsiella pneumoniae strain that typed to the sequence type 14 complex. The isolate, Klebsiella pneumoniae 05-506, was shown to possess a metallo- -lactamase (MBL) but was negative for previously known MBL genes. Gene libraries and amplification of class 1 integrons revealed three resistance- conferring regions; the first contained bla CMY-4 flanked by IS EcP1 and blc . The second region of 4.8 kb contained a complex class 1 integron with the gene cassettes arr- 2 , a new erythromycin esterase gene; ereC ; aadA1 ; and cmlA7 . An intact IS CR1 element was shown to be downstream from the qac / sul genes. The third region consisted of a new MBL gene, designated bla NDM-1 , flanked on one side by K. pneumoniae DNA and a truncated IS 26 element on its other side. The last two regions lie adjacent to one another, and all three regions are found on a 180-kb region that is easily transferable to recipient strains and that confers resistance to all antibiotics except fluoroquinolones and colistin. NDM-1 shares very little identity with other MBLs, with the most similar MBLs being VIM-1/VIM-2, with which it has only 32.4% identity. As well as possessing unique residues near the active site, NDM-1 also has an additional insert between positions 162 and 166 not present in other MBLs. NDM-1 has a molecular mass of 28 kDa, is monomeric, and can hydrolyze all-lactams except aztreonam. Compared to VIM-2, NDM-1 displays tighter binding to most cephalosporins, in particular, cefuroxime, cefotaxime, and cephalothin (cefalotin), and also to the penicillins. NDM-1 does not bind to the carbapenems as tightly as IMP-1 or VIM-2 and turns over the carbapenems at a rate similar to that of VIM-2....
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This note was uploaded on 12/03/2010 for the course PHAMACOLOG pcl470 taught by Professor Arnot during the Fall '10 term at University of Toronto- Toronto.

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J.Matthews_paper_for discussion1 - A NTIMICROBIAL AGENTS...

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